Diagnostic In Vivo and In Vitro Methods in Insect Allergy

The diagnosis of immediate-type hypersensitivity to Hymenoptera venom begins with a clinical history of an insect sting-induced large local or systemic reaction. This is followed by confirmation of sensitization to one or more medically important Hymenoptera venoms using in vivo (intradermal or epicutaneous skin test) and in vitro (IgE antibody serology, basophil activation, or mediator release) assays. Each of these confirmatory modalities has their strengths and limitations which are overviewed within the context of currently available technology. These confirmatory tests are, however, not perfect as there are patients with a convincing sting reaction history who have negative IgE antibody confirmatory test results and others with positive confirmatory tests who manifest no symptoms upon a Hymenoptera sting. This discordance between the patient’s clinical history and confirmatory test results occurs as a result of multiple factors that are related to the heterogeneous composition of venom allergen preparations employed, variability in the design and performance of testing methods, and differences in data analysis, positive threshold criteria, and interpretation methods. The insect sting challenge is considered the gold standard diagnostic test. However, due to logistic challenges of timely procurement of appropriate insects and potential safety concerns, it is rarely used except in research studies. Recent advances in molecular allergology have permitted the production of recombinant venom allergens that will supplement complex venom extracts and provide clarity in the future to patient sensitization patterns that are confounded by cross-reactivity resulting from common carbohydrate or protein epitopes that occur across venom species.